Materials and methods for the prevention and treatment of viral respiratory diseases

Abstract

This disclosure is related to the use of a peptide with antimicrobial properties. The peptide is administered topically via nasal or pulmonary delivery to prevent or treat respiratory diseases caused by viruses. A variety of formulations and uses are described as well as methods of manufacture thereof. The formulations are safe and useful in patients—both humans and animals—for the delivery of appropriate bioactive substance(s) to the respiratory system.

What is claimed is: 
     
         1 . A method of treating or preventing a viral respiratory disease, the method comprising administering to a subject in need thereof a peptide comprising the amino acid sequence of Peptide 346-001 or variant thereof comprising one, two, or three amino acid substitutions, wherein the administration is via intranasal or pulmonary routes of administration. 
     
     
         2 . The method of  claim 1 , wherein the peptide comprises the amino acid sequence of Peptide 346-001. 
     
     
         3 . The method of  claim 1 , wherein the peptide comprises the amino acid sequence of Peptide 346-001 having one, two, or three amino acid substitutions, the substitutions being selected from the following: the S at position 1 is substituted with K, D, A, N, M, T, or V; the W at position 2 is substituted with I, Y, F, P, L, V, H, M, A, T, or S; the L at position 3 is substituted with W, I, M, V, F, M, A, or T; the R at position 4 is substituted with C, K, Q, H, P, or C; the D at position 5 is substituted with R, I, E, N, or Y; the I at position 6 is substituted with W, V, L, or F; the W at position 7 is substituted with V, Y, F, P, L, V, H, or D; the D at position 8 is substituted with S, E, N, Y, or S; the W at position 9 is substituted with L, Y, F, P, L, V, or H; the I at position 10 is substituted with V, L, or F; the C at position 11 is substituted with S, A, P, M, H, or T; the E at position 12 is substituted with D, S, Q, Y, or T; the V at position 13 is substituted with F, I, L, A, F, or M; the L at position 14 is substituted with V, I, M, or F; the S at position 15 is substituted with D, A, N, T, Y, or P; the D at position 16 is substituted with E, N, Y, or S; the F at position 17 is substituted with W, Y, L, P, or H; or the K at position 18 is substituted with E, R, H, R, P, or Q. 
     
     
         4 . The method of any one of  claims 1 - 3 , wherein the peptide is modified with a lipophilic moiety via a linker bonded to a lysine, serine, or cysteine of the peptide or variant. 
     
     
         5 . The method of any one of  claims 1  to  4 , wherein the viral respiratory disease is a coronavirus infection, an influenza infection, or a respiratory syncytial virus (RSV) infection. 
     
     
         6 . The method of any one of  claims 1  to  5 , wherein the viral respiratory disease is a coronavirus infection. 
     
     
         7 . The method of any one of  claims 1  to  5 , wherein the viral respiratory disease is an influenza infection. 
     
     
         8 . The method of any one of  claims 1  to  5 , wherein the viral respiratory disease is a respiratory syncytial virus (RSV) infection. 
     
     
         9 . The method of any one of  claims 1  to  6 , wherein the viral respiratory disease is SARS-CoV-2 infection. 
     
     
         10 . The method of any one of  claims 1  to  9 , further comprising administering one or more complementary agents. 
     
     
         11 . A method of treating or preventing a viral respiratory disease, the method comprising administering to a subject in need thereof a peptide comprising
 X 1 -X 2 -X 3 -X 4 -X 5 -X 6 -X 7 -X 8 -X 9 -X 10 -X 11 -X 12 -X 13 -X 14 -X 15 -X 16 -X 17 -X 18  (Formula 1), wherein X, is S, K, D, A, N, M, T, or V; X 2  is W, I, Y, F, P, L, V, H, M, A, T, or S; X 3  is L, W, I, M, V, F, M, A, or T; X 4  is R, C, K, Q, H, P, or C; X 5  is D, R, I, E, N, or Y; X 6  is I, W, V, L, or F; X 7  is W, V, Y, F, P, L, V, H, or D; X 8  is D, S, E, N, Y, or S; X 9  is W, L, Y, F, P, L, V, or H; X 10  is I, V, L, or F; X 11  is C, S, A, P, M, H, or T; X 12  is E, D, S, Q, Y, or T; X 13  is V, F, I, L, A, F, or M; X 14  is L, V, I, M, or F; X 15  is S, D, A, N, T, Y, or P; X 16  is D, E, N, Y, or S; X 17  is F, W, Y, L, P, or H; and X 18  is K, E, R, H, R, P, or Q, wherein the administration is via intranasal or pulmonary routes of administration.   
     
     
         12 . The method of  claim 11 , wherein the peptide comprises an amino acid sequence set forth in Table 1. 
     
     
         13 . The method of  claim 11  or  claim 12 , wherein the viral respiratory disease is a coronavirus infection, an influenza infection, or a respiratory syncytial virus (RSV) infection. 
     
     
         14 . The method of  claim 13 , wherein the viral respiratory disease is a coronavirus infection. 
     
     
         15 . The method of  claim 13 , wherein the viral respiratory disease is an influenza infection. 
     
     
         16 . The method of  claim 13 , wherein the viral respiratory disease is SARS-CoV-2 infection. 
     
     
         17 . The method of any one of  claims 11  to  16 , wherein the viral respiratory disease is SARS-CoV-2 infection. 
     
     
         18 . The method of any one of  claims 11  to  17 , further comprising administering one or more complementary agents. 
     
     
         19 . The method of any one of  claims 11  to  18 , wherein the peptide is modified with a lipophilic moiety via a linker bonded to a lysine, serine, or cysteine of the peptide or variant. 
     
     
         20 . The method of any one of  claims 11  to  19 , wherein X 11  is not C. 
     
     
         21 . The method of any one of  claims 11  to  20 , wherein one or more amino acids are D-amino acids.